Selected from: Chinese Journal of Obstetrics and Gynecology, vol.55, No.2, February 2020
Author: Liang Donglin Ying, Li Hang, Hu Ping, Xu Zhengfeng
Prenatal diagnosis center of Nanjing Medical University maternity hospital 210004
Correspondence Author: Xu Zhengfeng, email: Zhengfeng
Abstract
objective
By analyzing the follow-up data of free DNA (CF DNA) test results in maternal peripheral blood and the related pregnancy outcomes, the value of CF DNA test in prenatal screening was evaluated.
Method
The clinical data of pregnant women who underwent CF DNA test in the maternity hospital affiliated to Nanjing Medical University from August 2011 to December 2017 were collected, including the general situation of pregnant women, CF DNA test results and follow-up results. The results of CF DNA test were analyzed for the pregnancy outcomes of high-risk and low-risk pregnant women with common trisomy (including trisomy 21, trisomy 18 and trisomy 13). The value of CF DNA test was evaluated, including sensitivity, specificity, positive predictive value and negative predictive value.
Result
(1) In this study, 43615 cases of pregnant women with CF? DNA test were included, of which 44 (0.10%, 44 / 43615) failed to test; the detection results were 314 (0.72%, 314 / 43571), 43257 (99.28%, 43257 / 43571) with common trisomy high risk.
(2) 277 (88.21%, 277 / 314) of 314 pregnant women with common trisomy and high risk of CF? DNA detection completed the follow-up, among which 228 (82.31%, 228 / 277) pregnant women received invasive prenatal diagnosis of 43257 pregnant women with low risk, 36826 (85.13%, 36826 / 43257) completed the follow-up, of which 572 (1.55%, 572 / 36 826) poor pregnancy outcome, including 4 cases with false negative results of CF DNA test. (3) The sensitivity of trisomy 21, trisomy 18 and trisomy 13 was 97.96%, 96.67% and 100.00%, the specificity was 99.96%, 99.95% and 99.95%, the positive predictive value was 90.57%, 63.04% and 17.39%, the negative predictive value was 99.99%, 99.98% and 100.00%, respectively.
conclusion
The detection of CF DNA has high sensitivity and specificity in the prenatal screening of common trisomy, but there are still a certain number of CF DNA detection results that pregnant women with high risk of common trisomy refuse to perform invasive prenatal diagnosis to verify the results of CF DNA detection. The common low-risk pregnant women with trisomy can not get the information of chromosome karyotype of fetus when some pregnant women have bad pregnancy outcome because of no invasive prenatal diagnosis.
Discussion
Since 1997, fetal cf-DNA has been confirmed to exist in maternal peripheral plasma [15], the detection of fetal chromosomal aneuploidy by maternal peripheral blood has been an important research direction in the field of prenatal screening. According to the follow-up results, this study evaluated the value of CF? DNA detection. Consistent with the relevant reports at home and abroad [6, 13, 16], the results of this study show that the detection of CF DNA has high sensitivity and specificity for the detection of common trisomy of fetal chromosomes, reflecting the advantages of this technology; and it is found that the inconsistency between the detection of CF DNA and the results of invasive prenatal diagnosis needs the attention of clinicians.
1、 Analysis of the follow-up results of high-risk pregnant women with common trisomy detected by CF? DNA
In 314 pregnant women with high risk of common trisomy detected by CF DNA, the overall positive predictive value of common trisomy detected by CF DNA for fetus was 77.63%, while the positive predictive value of trisomy 21, trisomy 18 and trisomy 13 was also different. The positive predictive value of trisomy 21 was the highest, followed by trisomy 18, and trisomy 13 was the lowest, which was similar to the results previously reported. Because the incidence of trisomy 18 and trisomy 13 is far lower than trisomy 21, it has an impact on the positive predictive value; in addition, the proportion of restricted placenta chimerism of trisomy 13 is significantly higher than trisomy 21 and trisomy 18, which may be the reason for the lowest positive predictive value of trisomy 13.
According to the relevant guidelines or consensus of many academic organizations at home and abroad, such as the American Association of Obstetricians and Gynaecologists (ACOG) and the American Society of medical genetics and genomics (ACMG), as a screening method, CF? DNA detection has a certain proportion of false positives. Therefore, pregnant women with high risk of common trisomy need to pass invasive prenatal diagnosis for high-risk results Line verification [18-19]. In this study, 5.77% (16 / 277) of pregnant women were found to terminate their pregnancy without any examination. Therefore, it is suggested to strengthen the consultation before and after the CF DNA test so that pregnant women can have a more accurate understanding of the CF DNA test. At present, the main reasons for the Inconformity between the results of CF? DNA detection and the results of invasive prenatal diagnosis of high-risk trisomy pregnant women include: restricted placental chimerism, fetal chimerism, chromosomal abnormality in the mother, one of the twins' embryo stop development and chromosomal copy number variation in the fetus. However, because the detection of CF? DNA is aimed at the evaluation of common chromosomal aneuploidy in fetus, most pregnant women think that the results of fetal chromosome karyotype are enough, and refuse to carry out further genetic detection, which limits the in-depth study on the causes of these inconsistent results.
2、 Analysis of the follow-up results of low-risk pregnant women with common trisomy detected by CF? DNA
In 36826 cases of low-risk women with common chromosome trisomy detected by CF? DNA, 1.55% of them had poor pregnancy outcome, including abortion, abnormal direct induction of labor by ultrasound and neonatal death. Only a few of them chose prenatal diagnosis. However, studies have shown that abortion and ultrasound examination of fetal structural abnormalities are closely related to chromosomal abnormalities. Therefore, the absence of chromosomal aneuploidy in this part of pregnant women with poor pregnancy outcome may affect the evaluation of the sensitivity, specificity and other detection technical parameters of CF? DNA detection, and more importantly, these information will help pregnant women to get pregnant again Genetic counseling. It should be emphasized that "low risk of common trisomy in CF DNA test does not indicate normal pregnancy outcome" for pregnant women undergoing CF DNA test, and genetic consultation and further prenatal diagnosis should be carried out in time for abnormalities found in later prenatal examination.
In addition, four cases of false negative were found in the follow-up of pregnant women with common chromosomal aneuploidy and low risk. Three of them were found abnormal in the systematic ultrasound examination after the detection of CF? DNA, including one case with 18 false negative trisomy. The fetal ultrasound examination showed that the strong echo ring of fetal skull presented "lemon" sign, the cerebellum presented "banana" sign, spina bifida, cleft lip, congenital heart disease, etc Two cases (21 cases) were false negative in trisomy, and fetal ultrasound showed abnormalities such as nasal bone loss, ventricular septal defect and tetralogy of Fallot. It is suggested that ultrasonography is very important for low-risk pregnant women with common chromosomal aneuploidy detected by CF? DNA, which is also consistent with the relevant guidelines of the American Society of maternal and fetal medicine (SMFM) [21]. The analysis of the causes of these false negatives will contribute to the clinical practice of CF DNA detection.
3、 Lost visit rate
The follow-up of the results of CF DNA detection, especially the follow-up of low-risk pregnant women with common chromosomal aneuploidies, is an important guarantee for the quality control and tracking of CF DNA detection, and there are some difficulties in the implementation process. During the follow-up of this study, 14.84% of pregnant women refused to follow up or lost contact without obtaining follow-up information. However, it is worth noting that before and after the technical specification for prenatal screening and diagnosis of fetal free DNA in maternal peripheral blood [14] was issued at the end of 2016, the completion rate of follow-up increased from 81.59% to 95.49%. It shows that the introduction of the standard plays an important role in the consultation before and after the CF DNA test and the correct publicity of the test, promotes the successful follow-up of the results of the CF DNA test, and improves the quality of the test.
To sum up, the detection of CF DNA in maternal peripheral blood has better technical advantages in screening common chromosomal aneuploidies of fetus, but there are still inconsistencies between the detection results of CF DNA and the karyotype results of prenatal diagnosis. Therefore, it is necessary to re emphasize that CF DNA detection is a screening hand rather than a diagnostic measure, which also shows that standardizing the detection process of CF DNA is of great significance.
References: omitted
Editor: Jiang Qiqi